This invention provides new compounds that are useful as insecticides and acaricides, new synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds.
There is an acute need for new insecticides and acaricides. Insects and mites are developing resistance to the insecticides and acaricides in current use. At least 400 species of arthropods are resistant to one or more insecticides. The development of resistance to some of the older insecticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pyrethroid insecticides and acaricides. Therefore a need exists for new insecticides and acaricides, and particularly for compounds that have new or atypical modes of action.
A number of 3,5-diphenyl-1H-1,2,4-triazole derivatives have been described in the literature as having acaricidal activity (U.S. Pat. No. 5,482,951; JP 8092224, EP572142, JP 08283261). Nitro furanyl triazoles are described by L. E. Benjamin and H. R. Snyder as antimicrobials (J Heterocyclic Chem. 1976, 13, 1115) and by others as antibacterials (J Med. Chem. 1973, 16(4), 312; J Med. Chem. 1974, 17(7), 756). The present invention provides novel compounds with broad spectrum activity against mites and insects.
This invention provides novel compounds especially useful for the control of insects and mites.
More specifically, the invention provides novel insecticidally active compounds of the formula (1) 
wherein
Ar is phenyl, substituted phenyl, pyridyl, substituted pyridyl, or lower alkyl;
R1 is lower alkyl, cycloalkyl, phenyl, or substituted phenyl;
Q is thienyl, substituted thienyl, phenyl, substituted phenyl, pyridyl, or substituted pyridyl;
R2 is selected from H, lower alkyl, lower alkenyl, pyridyl, substituted pyridyl, pyrimidyl, substituted pyrimidyl, isoxazolyl, substituted isoxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl, thienyl, substituted thienyl, xe2x80x94(CH2)mR3, xe2x80x94CHxe2x95x90CHR3, xe2x80x94Cxe2x89xa1CR3, xe2x80x94CH2OR3, xe2x80x94CH2SR3, xe2x80x94CH2NR3R3, xe2x80x94OCH2R3, xe2x80x94SCH2R3,xe2x80x94
R3 is H, lower alkyl, haloalkyl, lower alkenyl, lower alkynyl, phenyl, or substituted phenyl;
m is 1 or2;
n is an integer from 2 to 6; or a phytologically acceptable acid addition salt thereof.
Preferred compounds of formula (1) include the following classes:
(1) Compounds of formula (1) wherein Ar is a group of the formula 
wherein R4and R5 are independently H, Cl, F, methyl, halomethyl, methoxy, or halomethoxy.
(2) Compounds of formula (1) wherein Ar is a group of the formula 
wherein R4 and R5 are independently H, Cl, F, methyl, halomethyl, methoxy, or halomethoxy.
(3) Compounds of class (1) and (2) wherein R4 and R5 are independently F or Cl.
(4) Compounds of class (1) and (2) wherein R4 and R5 are both F.
(5) Compounds of class (1) and (2) wherein R4 and R5 are both Cl.
(6) Compounds of class (1) and (2) wherein R4 is F and R5 is Cl.
(7) Compounds of formula (1), and particularly compounds of class (1), (2), (3), (4), (5) or (6) as defined above, wherein Q is a substituted thiophene.
(8) Compounds of formula (1), and particularly compounds of class (1), (2), (3), (4), (5) or (6) as defined above, wherein Q is a substituted phenyl.
(9) Compounds of formula (1), and particularly compounds of any one of classes (1) through (8) as defined above, wherein R2 is methyl.
(10) Compounds of formula (1), and particularly compounds of any one of classes (1) through (9) as defined above, wherein R2 is a phenyl or substituted phenyl.
(11) Compounds of formula (1), and particularly compounds of any one of classes (1) through (9) as defined above, wherein R2 is a thiophene or substituted thiophene.
The invention also provides new processes and intermediates for preparing compounds of formula (1) as well as new compositions and methods of use, which will be described in detail hereinafter.
Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.
The term xe2x80x9clower alkylxe2x80x9d refers to (C1-C6) straight hydrocarbon chains and (C3-C6) branched and cyclic hydrocarbon groups.
The terms xe2x80x9clower alkenylxe2x80x9d and xe2x80x9clower alkynylxe2x80x9d refer to (C2-C6) straight hydrocarbon chains and (C3-C6) branched hydrocarbon groups containing at least one double or triple bond, respectively.
The term xe2x80x9clower alkoxyxe2x80x9d refers to xe2x80x94Oxe2x80x94lower alkyl.
The terms xe2x80x9chalomethylxe2x80x9d, xe2x80x9chaloalkylxe2x80x9d, and xe2x80x9chaloalkenylxe2x80x9d refer to methyl, lower alkyl, and lower alkenyl groups substituted with one or more halo atoms.
The terms xe2x80x9chalomethoxyxe2x80x9d and xe2x80x9chaloalkoxyxe2x80x9d refer to methoxy and lower alkoxy groups substituted with one or more halo atoms.
The term xe2x80x9calkoxyalkylxe2x80x9d refers to a lower alkyl group substituted with a lower alkoxy group.
The term xe2x80x9calkoxyalkoxyxe2x80x9d refers to a lower alkoxy group substituted with a lower alkoxy group.
The terms xe2x80x9csubstituted naphthylxe2x80x9d, xe2x80x9csubstituted thienyl,xe2x80x9d xe2x80x9csubstituted pyrimidyl,xe2x80x9d xe2x80x9csubstituted pyrazolyl,xe2x80x9d xe2x80x9csubstituted pyridyl,xe2x80x9d and xe2x80x9csubstituted isoxazolylxe2x80x9d refer to the ring system substituted with one or more groups independently selected from halo, halo (C1-C4) alkyl, CN, NO2, (C1-C4) alkyl, (C3-C4) branched alkyl, phenyl, (C1-C4) alkoxy, or halo (C 1-C4) alkoxy.
The term xe2x80x9csubstituted phenylxe2x80x9d refers to a phenyl group substituted with one or more groups independently selected from halo, (C1-C10) alkyl, branched (C3-C6) alkyl, halo (C1-C7) alkyl, hydroxy (C1-C7) alkyl, (C1-C7) alkoxy, halo (C1-C7) alkoxy, phenoxy, phenyl, NO2, OH, CN, (C1-C4) alkanoyl, benzoyl, (C1-C4) alkanoyloxy, (C1-C4) alkoxycarbonyl, phenoxycarbonyl, or benzoyloxy.
Unless otherwise indicated, when it is stated that a group may be substituted with one or more substituents selected from an identified class, it is intended that the substituents may be independently selected from the class.
Synthesis
Compounds of formula (1) can be prepared by the methods illustrated in Scheme 1: 
wherein Ar is phenyl or substituted phenyl, Q, and R2 are defined as in formula (1) above. The sequence shown in Scheme 1 involves the coupling of acid chlorides of formula (2) with the amidrazone of formula (3). Preparation 1, hereinafter, illustrates preparation of an amidrazone of formula (3). The base used in the coupling could be any organic or inorganic base. Acid chlorides of formula (2) are prepared from corresponding carboxylic acids of formula (11) 
which are either commercially available or are readily made through known procedures. Examples 1 and 2, hereinafter, illustrate the coupling and cyclization utilizing the amidrazone of formula (3) to produce a triazole product of formula (1).
Preparation 1
The following steps illustrate preparation of the amidrazone of formula (3a) 
A. 2,6-difluorobenzenethioamide
Into a 3 L three necked round bottom flask equipped with a mechanical stirrer, dry ice condenser, dropping funnel, and outlet to a trap filled with bleach was added pyridine (550 mL), 2,6-difluorobenzonitrile (208 g, 1.50 mol), triethylamine (202 g, 279 mL, 2.0 mol), and sodium sulfide hydrate (521 g, 2.17 mol-broken into pieces small enough to fit into the flask). The temperature of the stirred mixture was lowered to approximately 5xc2x0 C. and to the slurry was added dropwise concentrated hydrochloric acid (143 g, 288 mL, 3.99 mol). An exotherm was noted and the rate of addition of the hydrochloric acid was such that the temperature of the reaction mixture did not exceed 25xc2x0 C. for a total addition time of 75 min. The cooling bath was removed and the slurry was allowed to warm to RT and to stir over night. The mixture was poured into water (2 L) and was extracted with ether (3xc3x97500 mL). The ether layer was washed with dilute sulfuric acid, water, brine, dried (MgSO4), and the solvent removed in vacuo to give 232 grams of crude product. The starting material was removed from the product via kugelrohr distillation to give 197 g (76%) of 2,6-difluorobenzenethioamide. This material was used without further purification.
B. S-methylthio-2,6-difluorobenzamidinium iodide
Into a 3 L three necked flask equipped with a mechanical stirrer and dropping funnel was added acetone (1150 mL) and 2,6-difluorobenzenethioamide (197 g, 1.14 mol). The temperature of the stirred solution was lowered to approximately 5xc2x0 C. and iodomethane (161 g, 70.6 mL, 1.14 mol) was added dropwise. The ice bath was removed and the slurry was allowed to stir over night. The resulting yellow solids were removed via filtration and washed with ether to obtain 223 grams. An additional portion of material was obtained from the filtrate by removal of the solvent in vacuo. Ether was added to the residue and the resulting solids removed via filtration to obtain an additional 57 grams of material. The combined solids totaled 280 g (77.9% yield) of S-methylthio-2,6-difluoro-benzimidinium iodide: mp 168-169xc2x0 C.; 1H NMR (DMSO-d6) xcex47.7 (m, 1H), 7.4 (m, 2H), 2.7 (s, 3H).
C. N-tert-butoxvcarbonyl-N-methylhydrazine
Into a 1 L three necked round bottom flask equipped with a mechanical stirrer and dropping funnel was added methyl hydrazine (42.2 g, 0.916 mol) and THF (100 mL). The temperature of the mixture was cooled to 5xc2x0 C. and a solution of di-tert-butyl dicarbonate (100 g, 0.458 mol) dissolved in THF (150 mL) was added dropwise. The cooling bath was removed and the mixture was stirred at RT overnight. The liquid was decanted from a gummy precipitate and the solvent removed in vacuo to give approximately 70 grams of a clear liquid. The gummy precipitate was partitioned between methylene chloride and water. The methylene chloride was washed with brine, dried (Na2SO4) and the solvent removed in vacuo. The resulting residue was combined with that from the previous evaporation and distilled at approximately 20 mm Hg (bp 77-78xc2x0 C.) to give 40.2 g (60% yield) of N-tert-butoxycarbonyl-N-methylhydrazine: 1H NMR (CDCl3) 6 4.1 (bs, 2H), 3.05 (s, 3H), 1.5 (s, 9H).
D. Amidrazone of formula (3a)
Into a 1 L round bottom flask equipped with a mechanical stirrer, dropping funnel, and outlet to a trap filled with bleach, was added S-methyl-2,6-difluorobenziminium iodide (63.8 g, 0.202 mol) and methanol (180 mL). To the stirred solution was added dropwise N-tert-butoxycarbonyl-N-methylhydrazine (29.6 g. 0.202 mol). The solution was allowed to stir overnight and the methanol was removed in vacuo. The residue was triturated with ether and the solids removed via filtration to give 66.3 grams (79.0% yield) of the amidrazone of formula (3a): mp 172-173xc2x0 C. (dec); 1H NMR (DMSO-d6) xcex412.3 (s, b, 1H), 10.4 (d, b, 2H), 7.9 (m, 1H), 7.4 (m, 2H), 3.1 (s, 3H), 1.5 (s, 9H).